scholarly journals Erratum: Corrigendum: Tonic inhibition in dentate gyrus impairs long-term potentiation and memory in an Alzheimer’s disease model

2014 ◽  
Vol 5 (1) ◽  
Author(s):  
Zheng Wu ◽  
Ziyuan Guo ◽  
Marla Gearing ◽  
Gong Chen
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dentate Gyrus ◽  
Disease Model ◽  
Long Term Potentiation ◽  
Tonic Inhibition ◽  
Term Potentiation

scholarly journals Unexpected Early Proteomic Changes in Alzheimer’s Disease Model Mice Synaptosomes

2017 ◽  
Author(s):  
Kerri Ball ◽  
Addolorata Pisconti ◽  
Kelly Grounds ◽  
William M. Old ◽  
Michael H. B. Stowell
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Model ◽  
Long Term Potentiation ◽  
Label Free ◽  
Amyloid Accumulation ◽  
Term Potentiation ◽  
Novel Associations ◽  
Statistical Criteria

AbstractWe have employed label-free quantitative proteomics of wild-type and Alzheimer’s disease (AD) model mice synaptosomes to investigate proteomic changes occurring during AD progression as a prelude to analysis in humans. More than 4000 proteins were analyzed using multiple analysis tools and statistical criteria. Pathway enrichment identified numerous pathways consistent with the current AD knowledge base, including dysregulation of Glutamate Receptor Signaling, Synaptic Long Term Potentiation and Depression, Rho and Rac Signaling, Calcium Signaling, and Oxidative Phosphorylation and Mitochondrial Dysfunction. Additionally, the data demonstrate that a large number of changes occur in the proteome very early relative to the onset of both traditional disease markers such as amyloid accumulation, tau phosphorylation and cognitive dysfunction. These early changes include a number of dysregulated proteins that have novel associations with AD progression. These results reinforce the importance of mechanistic investigations in early disease progression long before the classical markers of Alzheimer’s disease are observed.

Neuroprotective properties of mitochondria-targeted antioxidants of the SkQ-type

2016 ◽  
Vol 27 (8) ◽  
pp. 849-855 ◽  
Author(s):  
Nickolay K. Isaev ◽  
Elena V. Stelmashook ◽  
Elisaveta E. Genrikhs ◽  
Galina A. Korshunova ◽  
Natalya V. Sumbatyan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Area ◽  
Hippocampal Slices ◽  
Amyloid Β ◽  
Long Term Potentiation ◽  
Term Potentiation ◽  
Neuroprotective Action

AbstractIn 2008, using a model of compression brain ischemia, we presented the first evidence that mitochondria-targeted antioxidants of the SkQ family, i.e. SkQR1 [10-(6′-plastoquinonyl)decylrhodamine], have a neuroprotective action. It was shown that intraperitoneal injections of SkQR1 (0.5–1 μmol/kg) 1 day before ischemia significantly decreased the damaged brain area. Later, we studied in more detail the anti-ischemic action of this antioxidant in a model of experimental focal ischemia provoked by unilateral intravascular occlusion of the middle cerebral artery. The neuroprotective action of SkQ family compounds (SkQR1, SkQ1, SkQTR1, SkQT1) was manifested through the decrease in trauma-induced neurological deficit in animals and prevention of amyloid-β-induced impairment of long-term potentiation in rat hippocampal slices. At present, most neurophysiologists suppose that long-term potentiation underlies cellular mechanisms of memory and learning. They consider inhibition of this process by amyloid-β1-42as anin vitromodel of memory disturbance in Alzheimer’s disease. Further development of the above studies revealed that mitochondria-targeted antioxidants could retard accumulation of hyperphosphorylated τ-protein, as well as amyloid-β1-42, and its precursor APP in the brain, which are involved in developing neurodegenerative processes in Alzheimer’s disease.

scholarly journals Progressive Age-Related Impairment of the Late Long-Term Potentiation in Alzheimer's Disease Presenilin-1 Mutant Knock-in Mice

2010 ◽  
Vol 19 (3) ◽  
pp. 1021-1033 ◽  
Author(s):  
Alexandra Auffret ◽  
Vanessa Gautheron ◽  
Mark P. Mattson ◽  
Jean Mariani ◽  
Catherine Rovira
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Long Term Potentiation ◽  
Presenilin 1 ◽  
Age Related ◽  
Term Potentiation

scholarly journals TDP-43 interacts with amyloid-β, inhibits fibrillization, and worsens pathology in a model of Alzheimer’s disease

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Yao-Hsiang Shih ◽  
Ling-Hsien Tu ◽  
Ting-Yu Chang ◽  
Kiruthika Ganesan ◽  
Wei-Wei Chang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Long Term Potentiation ◽  
Model Of Alzheimer’S Disease ◽  
Term Potentiation ◽  
Spatial Memory Deficit ◽  
Aβ Aggregation ◽  
Intrahippocampal Injection

AbstractTDP-43 inclusions are found in many Alzheimer’s disease (AD) patients presenting faster disease progression and greater brain atrophy. Previously, we showed full-length TDP-43 forms spherical oligomers and perturbs amyloid-β (Aβ) fibrillization. To elucidate the role of TDP-43 in AD, here, we examined the effect of TDP-43 in Aβ aggregation and the attributed toxicity in mouse models. We found TDP-43 inhibited Aβ fibrillization at initial and oligomeric stages. Aβ fibrillization was delayed specifically in the presence of N-terminal domain containing TDP-43 variants, while C-terminal TDP-43 was not essential for Aβ interaction. TDP-43 significantly enhanced Aβ’s ability to impair long-term potentiation and, upon intrahippocampal injection, caused spatial memory deficit. Following injection to AD transgenic mice, TDP-43 induced inflammation, interacted with Aβ, and exacerbated AD-like pathology. TDP-43 oligomers mostly colocalized with intracellular Aβ in the brain of AD patients. We conclude that TDP-43 inhibits Aβ fibrillization through its interaction with Aβ and exacerbates AD pathology.

scholarly journals Cyclase-associated protein 2 dimerization regulates cofilin in synaptic plasticity and Alzheimer's disease

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Silvia Pelucchi ◽  
Lina Vandermeulen ◽  
Lara Pizzamiglio ◽  
Bahar Aksan ◽  
Jing Yan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Actin Cytoskeleton ◽  
Structural Plasticity ◽  
Long Term Potentiation ◽  
Brain Diseases ◽  
Biological Trait ◽  
Term Potentiation ◽  
Cytoskeleton Dynamics

Abstract Regulation of actin cytoskeleton dynamics in dendritic spines is crucial for learning and memory formation. Hence, defects in the actin cytoskeleton pathways are a biological trait of several brain diseases, including Alzheimer's disease. Here, we describe a novel synaptic mechanism governed by the cyclase-associated protein 2, which is required for structural plasticity phenomena and completely disrupted in Alzheimer's disease. We report that the formation of cyclase-associated protein 2 dimers through its Cys32 is important for cyclase-associated protein 2 binding to cofilin and for actin turnover. The Cys32-dependent cyclase-associated protein 2 homodimerization and association to cofilin are triggered by long-term potentiation and are required for long-term potentiation-induced cofilin translocation into spines, spine remodelling and the potentiation of synaptic transmission. This mechanism is specifically affected in the hippocampus, but not in the superior frontal gyrus, of both Alzheimer's disease patients and APP/PS1 mice, where cyclase-associated protein 2 is down-regulated and cyclase-associated protein 2 dimer synaptic levels are reduced. Notably, cyclase-associated protein 2 levels in the cerebrospinal fluid are significantly increased in Alzheimer's disease patients but not in subjects affected by frontotemporal dementia. In Alzheimer's disease hippocampi, cofilin association to cyclase-associated protein 2 dimer/monomer is altered and cofilin is aberrantly localized in spines. Taken together, these results provide novel insights into structural plasticity mechanisms that are defective in Alzheimer's disease.

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